Mystery of Tau Tangle Spread in Alzheimer's Unraveled

Author: Jeannette Y. Wick, RPh, MBA, FASCP

New treatments for Alzheimer’s disease could spring from the discovery of how tau protein tangles spread through the brain.
Tangles of tau protein have been associated with Alzheimer’s disease (AD) for decades, but exactly how they spread throughout the brain has been a mystery. Researchers have long observed that dying, tau-filled cells first appear in AD patients’ entorhinal cortex, a small area of the brain believed to create and store memories. From there, they slowly creep outward and spread throughout the brain, ultimately destroying memory, reasoning, and the ability to function. Within 7 to 10 years, the patient dies.

To explain how this spread occurs, there have been two competing hypotheses: (1) the disease is passed from neuron to neuron, or (2) different areas of the brain have different levels of resilience in the face of the disease, and the less resilient areas are affected first. Two recently published studies—one in PLoS one and one in Neuron—have provided significant support for the first of these hypotheses.

In both studies, researchers genetically engineered mice to produce abnormal human tau proteins in the entorhinal region, but nowhere else in the brain. As expected, the researchers first observed tau tangles in the entorhinal cells. They then observed tau protein spreading along neuronal networks, destroying cells as they went. Since these cells—outside the entorhinal region—could not make their own human tau, but were becoming infected nonetheless, the researchers had clear evidence that the disease spreads from neuron to neuron.

The researchers suspect that their observations of the spread of tau in mice will hold for humans as well and may point the way to treatment of AD with a tau-blocking antibody that could stop transmission of the protein between cells. In addition, they suspect that other degenerative brain diseases, such as Parkinson’s, may spread in a similar way, passing bad protein from cell-to-cell.

Ms. Wick is a visiting professor at the University of Connecticut School of Pharmacy and a freelance writer from Virginia.